Volumetric quantitative optical coherence elastography with an iterative inversion method

It is widely accepted that accurate mechanical properties of three-dimensional soft tissues and cellular samples are not available on the microscale. Current methods based on optical coherence elastography can measure displacements at the necessary resolution, and over the volumes required for this task. However, in converting this data to maps of elastic properties, they often impose assumptions regarding homogeneity in stress or elastic properties that are violated in most realistic scenarios. Here, we introduce novel, rigorous, and computationally efficient inverse problem techniques that do not make these assumptions, to realize quantitative volumetric elasticity imaging on the microscale. Specifically, we iteratively solve the threedimensional elasticity inverse problem using displacement maps obtained from compression optical coherence elastography. This is made computationally feasible with adaptive mesh refinement and domain decomposition methods. By employing a transparent, compliant surface layer with known shear modulus as a reference for the measurement, absolute shear modulus values are produced within a millimeter-scale sample volume. We demonstrate the method on phantoms, on an ex vivo breast cancer sample, and in vivo on human skin. Quantitative elastography on this length scale will find wide application in cell biology, tissue engineering and medicine

Different level of population differentiation among human genes

<p>Abstract</p> <p>Background</p> <p>During the colonization of the world, after dispersal out of African, modern humans encountered changeable environments and substantial phenotypic variations that involve diverse behaviors, lifestyles and cultures, were generated among the different modern human populations.</p> <p>Results</p> <p>Here, we study the level of population differentiation among different populations of human genes. Intriguingly, genes involved in osteoblast development were identified as being enriched with higher <it>F</it>_STSNPs, a result consistent with the proposed role of the skeletal system in accounting for variation among human populations. Genes involved in the development of hair follicles, where hair is produced, were also found to have higher levels of population differentiation, consistent with hair morphology being a distinctive trait among human populations. Other genes that showed higher levels of population differentiation include those involved in pigmentation, spermatid, nervous system and organ development, and some metabolic pathways, but few involved with the immune system. Disease-related genes demonstrate excessive SNPs with lower levels of population differentiation, probably due to purifying selection. Surprisingly, we find that Mendelian-disease genes appear to have a significant excessive of SNPs with high levels of population differentiation, possibly because the incidence and susceptibility of these diseases show differences among populations. As expected, microRNA regulated genes show lower levels of population differentiation due to purifying selection.</p> <p>Conclusion</p> <p>Our analysis demonstrates different level of population differentiation among human populations for different gene groups.</p

New ruthenium complexes of fullerene C-60&C-70

The new complexes [Ru(NO)(PPh3)](2)(eta(2)-C-m)(m=60 1 or 70 2) have been prepared by heating a solution of C-60(or C-70) with [Ru(NO)(2)(PPh3)(2)] in toluene. They have been characterized by elemental analysis, IR, UV/VIS, XPS, C-13 and P-31 NMR spectroscopy. The photovaltaic effect for the new compounds has been studied

Reduced growth and proliferation dynamics of nasal epithelial stem/progenitor cells in nasal polyps in vitro

10.1038/srep04619Scientific Reports4

RASSF1A–LATS1 signalling stabilizes replication forks by restricting CDK2-mediated phosphorylation of BRCA2

Genomic instability is a key hallmark of cancer leading to tumour heterogeneity and therapeutic resistance. ​BRCA2 has a fundamental role in error-free DNA repair but also sustains genome integrity by promoting ​RAD51 nucleofilament formation at stalled replication forks. ​CDK2 phosphorylates ​BRCA2 (pS3291-​BRCA2) to limit stabilizing contacts with polymerized ​RAD51; however, how replication stress modulates ​CDK2 activity and whether loss of pS3291-​BRCA2 regulation results in genomic instability of tumours are not known. Here we demonstrate that the Hippo pathway kinase ​LATS1 interacts with ​CDK2 in response to genotoxic stress to constrain pS3291-​BRCA2 and support ​RAD51 nucleofilaments, thereby maintaining genomic fidelity during replication stalling. We also show that ​LATS1 forms part of an ​ATR-mediated response to replication stress that requires the tumour suppressor ​RASSF1A. Importantly, perturbation of the ​ATR–​RASSF1A–​LATS1 signalling axis leads to genomic defects associated with loss of ​BRCA2 function and contributes to genomic instability and ‘BRCA-ness’ in lung cancers

The right vertical infra-axillary incision for mitral valve replacement

<p>Abstract</p> <p>Background</p> <p>As the physiologic results of valve surgery have improved dramatically in recent years, the cosmetic effect of the procedure gains increased attention, and various alternatives to the standard median sternotomy have been developed for mitral valve surgery. We report a new minimally invasive and cosmetic approach for mitral valve replacement.</p> <p>Methods</p> <p>From December 2003 to December 2009, the right vertical infra-axillary incision (RVIAI) was employed to perform mitral valve replacement in 256 patients. 62.9% patients had replaced mechanical valve, others were bioprosthetic valve, at the same time 28.1% patients received tricuspid valvuloplasty.</p> <p>Results</p> <p>There were one hospital death in this series due to multiple organ failure, one reoperation for bleeding and one incision infection. Mean follow-up duration was 42.8 months (range, 3 to 72), and follow-up rate was 94%. There were no paravalvular leaks or late death during the follow up.</p> <p>Conclusions</p> <p>The RVIAI can be performed with favorable cosmetic and clinical results. It provides a good alternative to standard median sternotomy for MVR in selected patients.</p

Evidence for Positive Selection on the Osteogenin (BMP3) Gene in Human Populations

BACKGROUND: Human skeletal system has evolved rapidly since the dispersal of modern humans from Africa, potentially driven by selection and adaptation. Osteogenin (BMP3) plays an important role in skeletal development and bone osteogenesis as an antagonist of the osteogenic bone morphogenetic proteins, and negatively regulates bone mineral density. METHODOLOGY/PRINCIPAL FINDINGS: Here, we resequenced the BMP3 gene from individuals in four geographically separated modern human populations. Features supportive of positive selection in the BMP3 gene were found including the presence of an excess of nonsynonymous mutations in modern humans, and a significantly lower genetic diversity that deviates from neutrality. The prevalent haplotypes of the first exon region in Europeans demonstrated features of long-range haplotype homogeneity. In contrast with findings in European, the derived allele SNP Arg192Gln shows higher extended haplotype homozygosity in East Asian. The worldwide allele frequency distribution of SNP shows not only a high-derived allele frequency in Asians, but also in Americans, which is suggestive of functional adaptation. CONCLUSIONS/SIGNIFICANCE: In conclusion, we provide evidence for recent positive selection operating upon a crucial gene in skeletal development, which may provide new insight into the evolution of the skeletal system and bone development

In Silico Elucidation of the Recognition Dynamics of Ubiquitin

Elucidation of the mechanism of biomacromolecular recognition events has been a topic of intense interest over the past century. The inherent dynamic nature of both protein and ligand molecules along with the continuous reshaping of the energy landscape during the binding process renders it difficult to characterize this process at atomic detail. Here, we investigate the recognition dynamics of ubiquitin via microsecond all-atom molecular dynamics simulation providing both thermodynamic and kinetic information. The high-level of consistency found with respect to experimental NMR data lends support to the accuracy of the in silico representation of the conformational substates and their interconversions of free ubiquitin. Using an energy-based reweighting approach, the statistical distribution of conformational states of ubiquitin is monitored as a function of the distance between ubiquitin and its binding partner Hrs-UIM. It is found that extensive and dense sampling of conformational space afforded by the µs MD trajectory is essential for the elucidation of the binding mechanism as is Boltzmann sampling, overcoming inherent limitations of sparsely sampled empirical ensembles. The results reveal a population redistribution mechanism that takes effect when the ligand is at intermediate range of 1–2 nm from ubiquitin. This mechanism, which may be depicted as a superposition of the conformational selection and induced fit mechanisms, also applies to other binding partners of ubiquitin, such as the GGA3 GAT domain

Nociception-induced spatial and temporal plasticity of synaptic connection and function in the hippocampal formation of rats: a multi-electrode array recording

<p>Abstract</p> <p>Background</p> <p>Pain is known to be processed by a complex neural network (neuromatrix) in the brain. It is hypothesized that under pathological state, persistent or chronic pain can affect various higher brain functions through ascending pathways, leading to co-morbidities or mental disability of pain. However, so far the influences of pathological pain on the higher brain functions are less clear and this may hinder the advances in pain therapy. In the current study, we studied spatiotemporal plasticity of synaptic connection and function in the hippocampal formation (HF) in response to persistent nociception.</p> <p>Results</p> <p>On the hippocampal slices of rats which had suffered from persistent nociception for 2 h by receiving subcutaneous bee venom (BV) or formalin injection into one hand paw, multisite recordings were performed by an 8 × 8 multi-electrode array probe. The waveform of the field excitatory postsynaptic potential (fEPSP), induced by perforant path electrical stimulation and pharmacologically identified as being activity-dependent and mediated by ionotropic glutamate receptors, was consistently positive-going in the dentate gyrus (DG), while that in the CA1 was negative-going in shape in naïve and saline control groups. For the spatial characteristics of synaptic plasticity, BV- or formalin-induced persistent pain significantly increased the number of detectable fEPSP in both DG and CA1 area, implicating enlargement of the synaptic connection size by the injury or acute inflammation. Moreover, the input-output function of synaptic efficacy was shown to be distinctly enhanced by the injury with the stimulus-response curve being moved leftward compared to the control. For the temporal plasticity, long-term potentiation produced by theta burst stimulation (TBS) conditioning was also remarkably enhanced by pain. Moreover, it is strikingly noted that the shape of fEPSP waveform was drastically deformed or split by a TBS conditioning under the condition of persistent nociception, while that in naïve or saline control state was not affected. All these changes in synaptic connection and function, confirmed by the 2-dimentional current source density imaging, were found to be highly correlated with peripheral persistent nociception since pre-blockade of nociceptive impulses could eliminate all of them. Finally, the initial pharmacological investigation showed that AMPA/KA glutamate receptors might play more important roles in mediation of pain-associated spatiotemporal plasticity than NMDA receptors.</p> <p>Conclusion</p> <p>Peripheral persistent nociception produces great impact upon the higher brain structures that lead to not only temporal plasticity, but also spatial plasticity of synaptic connection and function in the HF. The spatial plasticity of synaptic activities is more complex than the temporal plasticity, comprising of enlargement of synaptic connection size at network level, deformed fEPSP at local circuit level and, increased synaptic efficacy at cellular level. In addition, the multi-synaptic model established in the present investigation may open a new avenue for future studies of pain-related brain dysfunctions at the higher level of the neuromatrix.</p